scholarly journals Treatment of Adrenocorticotropin-Dependent Cushing’s Syndrome: A Consensus Statement

2008 ◽  
Vol 93 (7) ◽  
pp. 2454-2462 ◽  
Author(s):  
B. M. K. Biller ◽  
A. B. Grossman ◽  
P. M. Stewart ◽  
S. Melmed ◽  
X. Bertagna ◽  
...  
Keyword(s):  
Medical Therapy ◽  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Consensus Statement ◽  
Tumor Resection ◽  
Cushing's Syndrome ◽  
Scientific Data ◽  
Cushing's Disease ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth

Abstract Objective: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing’s syndrome, because there is no recent consensus on the management of this rare disorder. Participants: Thirty-two leading endocrinologists, clinicians, and neurosurgeons with specific expertise in the management of ACTH-dependent Cushing’s syndrome representing nine countries were chosen to address 1) criteria for cure and remission of this disorder, 2) surgical treatment of Cushing’s disease, 3) therapeutic options in the event of persistent disease after transsphenoidal surgery, 4) medical therapy of Cushing’s disease, and 5) management of ectopic ACTH syndrome, Nelson’s syndrome, and special patient populations. Evidence: Participants presented published scientific data, which formed the basis of the recommendations. Opinion shared by a majority of experts was used where strong evidence was lacking. Consensus Process: Participants met for 2 d, during which there were four chaired sessions of presentations, followed by general discussion where a consensus was reached. The consensus statement was prepared by a steering committee and was then reviewed by all authors, with suggestions incorporated if agreed upon by the majority. Conclusions: ACTH-dependent Cushing’s syndrome is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management. Generally, the treatment of choice for ACTH-dependent Cushing’s syndrome is curative surgery with selective pituitary or ectopic corticotroph tumor resection. Second-line treatments include more radical surgery, radiation therapy (for Cushing’s disease), medical therapy, and bilateral adrenalectomy. Because of the significant morbidity of Cushing’s syndrome, early diagnosis and prompt therapy are warranted.

Selective Venous Sampling for ACTH in Cushing’s Syndrome: Differentiation Between Cushing’s Disease and the Ectopic ACTH Syndrome

1982 ◽  
Vol 127 (3) ◽  
pp. 618-619
Author(s):  
J.W. Findling ◽  
D.C. Aron ◽  
J.B. Tyrrell ◽  
J.H. Shinsako ◽  
P.A. Fitzgerald ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Ectopic Acth Syndrome ◽  
Syndrome Differentiation ◽  
Venous Sampling ◽  
Ectopic Acth ◽  
Selective Venous Sampling

scholarly journals Cushing’s Syndrome: Important Issues in Diagnosis and Management

2006 ◽  
Vol 91 (10) ◽  
pp. 3746-3753 ◽  
Author(s):  
James W. Findling ◽  
Hershel Raff
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Evidence Synthesis ◽  
Somatostatin Receptor ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Late Night ◽  
Recent Monograph

Abstract Context: The diagnosis, differential diagnosis, and treatment of Cushing’s syndrome are challenging problems in clinical endocrinology. We focus on critical questions addressing screening for Cushing’s syndrome, differentiation of Cushing’s subtypes, and treatment options. Evidence Acquisition: Ovid’s MEDLINE (1996 through April 2006) was used to search the general literature. We also relied on previously published reviews and a recent monograph and cite a mix of primary articles and recent reviews. Evidence Synthesis: Although this article represents our opinion, it draws heavily on a recent consensus statement from experts in the field and a recent monograph on Cushing’s syndrome. Conclusions: We concluded that: 1) measurement of late-night or bedtime salivary cortisol is a useful approach to screen for Cushing’s syndrome; 2) measurement of suppressed plasma ACTH by immunometric assay is useful to differentiate ACTH-dependent and -independent Cushing’s syndrome; 3) inferior petrosal sinus sampling for ACTH should be performed in patients with ACTH-dependent hypercortisolism in whom a pituitary magnetic resonance imaging is normal or equivocal (in the absence of a pituitary ACTH gradient, prolactin levels should be measured to confirm the integrity of venous sampling); 4) computed tomography of the chest and abdomen and somatostatin receptor scintigraphy should be performed in patients with the occult ectopic ACTH syndrome; and 5) patients with Cushing’s disease should be referred to a neurosurgeon with extensive experience operating on corticotroph microadenomas. Bilateral laparoscopic adrenalectomy should be considered in patients with Cushing’s disease who fail therapies directed at the pituitary.

scholarly journals Intestinal Perforation in ACTH-Dependent Cushing’s Syndrome

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Mariam Shahidi ◽  
Richard A. Phillips ◽  
Constance L. Chik
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Intestinal Perforation ◽  
Urinary Free Cortisol ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Free Cortisol ◽  
Ectopic Acth Production

Previous studies have linked systemic glucocorticoid use with intestinal perforation. However, the association between intestinal perforation and endogenous hypercortisolism has not been well described, with only 14 previously published case reports. In this study, we investigated if intestinal perforation occurred more frequently in patients with ectopic ACTH syndrome and in those with a greater than 10-fold elevation of 24-hour urinary free cortisol level. Of 110 patients with ACTH-dependent Cushing’s syndrome followed in two clinics in Canada, six cases with intestinal perforation were identified over 15 years. Age of patients ranged from 52 to 72, five females and one male, four with Cushing’s disease and two with ectopic ACTH production, one from a pancreatic neuroendocrine tumor and one from medullary carcinoma of the thyroid. Five had diverticular perforation and one had intestinal perforation from a stercoral ulcer. All cases had their lower intestinal perforation when the cortisol production was high, and one patient had diverticular perforation 15 months prior to the diagnosis of Cushing’s disease. As in previously reported cases, most had hypokalemia and abdominal pain with minimal or no peritoneal symptoms and this occurred during the active phase of Cushing’s syndrome. Whereas all previously reported cases occurred in patients with 24-hour urinary free cortisol levels greater than 10-fold the upper limit of normal when measured and 11 of 14 patients had ectopic ACTH production, only one of our patients had this degree of hypercortisolism and four of our six patients had Cushing’s disease. Similar to exogenous steroid use, patients with endogenous hypercortisolism also have a higher risk of intestinal, in particular diverticular, perforation and should be monitored closely for its occurrence with a low threshold for investigation and surgical intervention. Elective colonoscopy probably should be deferred until Cushing’s syndrome is under control.

scholarly journals Intraoperative Adrenocorticotropin Levels During Transsphenoidal Surgery for Cushing’s Disease Do Not Predict Cure

1997 ◽  
Vol 82 (6) ◽  
pp. 1776-1779
Author(s):  
Kathryn E. Graham ◽  
Mary H. Samuels ◽  
Hershel Raff ◽  
Stanley L. Barnwell ◽  
David M. Cook
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Tumor ◽  
Transsphenoidal Surgery ◽  
Tumor Resection ◽  
Cushing's Disease ◽  
Ectopic Acth Syndrome ◽  
Plasma Acth ◽  
Tumor Removal ◽  
Ectopic Acth ◽  
Percentage Decrease

Abstract Recently, intraoperative rapid immunochemiluminometric assay (ICMA) ACTH measurements have been used to evaluate the completeness of resection of ectopic ACTH-secreting tumors. This study evaluates whether this method can be applied to patients undergoing transsphenoidal surgery (TSS) for Cushing’s disease to predict complete pituitary tumor resection. Eighteen patients with Cushing’s disease undergoing TSS had plasma ACTH concentrations measured by a standard ICMA every 10 min for 1 h immediately after pituitary tumor removal. Patients were evaluated postoperatively for cure by standard criteria. ACTH levels were evaluated for percentage decrease from baseline at each time point. Patients who were cured (n = 11) had statistically greater decreases in ACTH levels (mean decrease 54%) than patients who were not (n = 7; 26% mean decrease, P < 0.04). By Receiver-Operator Characteristic (ROC) analysis, a reduction of at least 40% best predicted which patients were cured and which were not cured. This level of reduction was observed in 82% of cured patients, and a reduction of less than 40% was observed in 71% of those not cured. The analysis misclassified 4 of the 18 patients, resulting in a diagnostic accuracy of 78%. Although the mean maximal decrease in ACTH concentrations after tumor removal was significantly different between cured and not cured patients with Cushing’s disease, it was less dramatic than results in the previous ectopic ACTH study. This may relate to incomplete suppression and/or surgical manipulation of normal pituitary corticotrophs in patients with pituitary disease. In summary, in contrast to the ectopic ACTH syndrome, decline of plasma ACTH during TSS does not accurately predict complete tumor resection.

scholarly journals The role of inferior petrosal sinus sampling in the diagnostic localization of Cushing's disease

2007 ◽  
Vol 23 (3) ◽  
pp. 1-6 ◽  
Author(s):  
Shivanand P. Lad ◽  
Chirag G. Patil ◽  
Edward R. Laws ◽  
Laurence Katznelson
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Treatment Decisions ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Inferior Petrosal Sinus ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Inferior Petrosal Sinus Sampling

✓ Cushing's syndrome can present a complex problem of differential diagnosis. Of cases in which hypercortisolemia results from an adrenocorticotropic hormone (ACTH)–dependent process, approximately 80% are due to a pituitary adenoma (Cushing's disease [CD]), 10% are due to adrenal lesions, and the remaining 10% are secondary to ectopic ACTH secretion. For patients with CD, surgical removal of the pituitary adenoma is the treatment of choice. Thus, localization of the source of ACTH secretion is critical in guiding timely treatment decisions. Inferior petrosal sinus sampling (IPSS) is considered to be the gold standard for confirming the origin of ACTH secretion in patients with Cushing's syndrome. The authors present an overview of IPSS—both the technique and its interpretation—as well as a summary of recent studies. A number of other techniques are discussed including sampling from the cavernous sinus, the jugular vein, and multiple sites to aid the diagnosis and lateralization of ACTH-producing pituitary adenomas. Management is best undertaken by a comprehensive multidisciplinary team taking into account the results of all the biochemical and imaging studies available, to provide the best advice in patient treatment decisions.

scholarly journals ACTH Dependent Cushing’s Syndrome: A 72-Hour Trial of Octreotide will Identify Patients with Pituitary Dependent and Ectopic ACTH Overproduction

2020 ◽  
pp. 65-70
Author(s):  
Omayma Elshafie ◽  
Nicholas Woodhouse
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Somatostatin Receptors ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Pituitary Tumours ◽  
Ectopic Acth ◽  
Suppression Test ◽  
Cortisol Levels

Aims: To determine whether the use of an octreotide suppression test will reliably distinguish pituitary from ectopic ACTH overproduction.  Somatostatin receptors are expressed in NETs, but are downgraded in the pituitary as the result of hypercortisolaemia. Octreotide should therefore lower ACTH and cortisol levels in patients with NETs but not in patients with Cushing’s disease and pituitary tumors. Methodology: A cross sectional study was performed in 13 patents with ACTH dependent Cushing’s (8 women, 5 men) with ages ranging between 21 to 40 years were studied. Serum cortisol concentrations were measured at 0800 hrs before and during the administration of. Octreotide at a dosage of 100 mcg subcutaneously every 8 hours for 72 hours. Results: The serum cortisol concentrations returned to normal in 4 patients who were later documented to have ectopic disease, two with typical bronchial carcinoids and two with pancreatic NETs and metastatic disease. The other 9 patients had no suppression in serum cortisol concentrations and were documented later to have pituitary tumours. Conclusion: These results indicate that a short trial of octreotide will identify patients with ectopic disease as evidenced by a fall in serum cortisol levels whereas in those with Cushing’s disease and pituitary tumours serum cortisol levels remains unchanged.  Recommendation: We recommend all patients with ACTH dependent Cushing’s syndrome have an octreotide suppression test, even if the MRI shows an adenoma, so as to exclude the possibility of a pituitary incidentaloma in a patient with ectopic disease, or false localization from IPSS to the pituitary gland due to ectopic CRH secretion.

scholarly journals Rapidly progressive ACTH-dependent Cushing’s disease masquerading as ectopic ACTH-producing Cushing’s syndrome: illustrative case

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Siyuan Yu ◽  
Michael Karsy ◽  
Jeffrey Miller ◽  
Stephanie R. Beldick ◽  
Mark T. Curtis ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cavernous Sinus ◽  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Rapid Evolution ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Illustrative Case ◽  
Ectopic Acth ◽  
Free Cortisol

BACKGROUND Cushing’s disease (CD) remains a challenging condition to diagnose and treat. This case study highlights the challenges of diagnosing CD when faced with discrepant clinical, biochemical, and radiological findings. OBSERVATIONS A 62-year-old man presented with rapid evolution of symptoms, including depression, fatigue, and extreme muscle atrophy, which resulted in the patient being a wheelchair user over the course of a few months. His rapid clinical course in conjunction with hypercortisolemia in the setting of a pituitary macroadenoma involving the cavernous sinus, two large pulmonary nodules, and urine-free cortisol levels in the thousands suggested an aggressive ectopic adrenocorticotropic hormone (ACTH) source. After extensive testing ruled out CD from an ectopic source and because of the patient’s abrupt clinical deterioration, the authors concluded that the source was likely an aggressive pituitary adenoma. Therefore, the authors performed an endonasal transsphenoidal approach for resection of the pituitary adenoma involving the cavernous sinus, and the patient was scheduled for radiosurgery to control tumor progression. LESSONS Although extremely high levels of cortisol and ACTH are associated with ectopic Cushing’s syndrome, they may also indicate an aggressive form of CD. Suspicion should be maintained for hypercortisolemia from a pituitary source even when faced with discrepant information that may suggest an ectopic source.

scholarly journals The Value of Ga68-DOTATATE PET/CT in Diagnosis and Management of Suspected Pituitary Tumors

2021 ◽  
Author(s):  
Fuad Novruzov ◽  
Aziz Aliyev ◽  
Ming Young S Wan ◽  
Rizwan Syed ◽  
Elnur Mehdi ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Somatostatin Receptor ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Receptor Subtype ◽  
Somatostatin Analogue ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Pet Ct

Abstract Backroud Gallium 68-tetraazacyclododecane-tetraacetic acid-octreotate (Ga-68‑DOTATATE) is a selective somatostatin analogue ligand, which shows increased affinity for somatostatin receptor subtype (SSTR) 2 and has been used routinely for imaging neuroendocrine tumors with PET/CT. We investigated the utility of ­­Ga-68‑DOTATATE positron emission tomography/computed tomography (PET/CT) in patients with suspected pituitary pathology. We reviewed imaging for twenty consecutive patients (8 men, 12 women, mean age of 48.2, range: 14-78) with suspected pituitary pathology who were referred for Ga-68-DOTATATE PET-CT. Results Nine patients presented with recurrent Cushing's syndrome following surgical resection of pituitary adenomas due to recurrent Cushing's disease (seven patients) and ectopic ACTH secreting tumor (2 patients). All seven patients with recurrent Cushing's disease showed positive pituitary Ga-68-DOTATATE uptake while both cases of ectopic hormonal secretion had absent pituitary uptake. In 1 of these 2 patients Ga-68-DOTATATE was able to localize the source of ectopic ACTH tumor. Six patients presented de novo with Cushing's due to ectopic ACTH secretion; Ga-68‑DOTATATE PET/CT was able to localize ectopic tumors in six of eight patients (3 lungs, 2 pancreases, 1 mid-gut) There was high uptake Ga-68-DOTATATE in 3 cases of recurrent central hyperthyroidism (SUVmax 6.6-14.3) and 2 cases of prolactinoma (SUVmax 5.5 and 11.3).Conclusion Absent Ga-68-DOTATATE activity in the pituitary fossa is useful in excluding pituitary disease in recurrent Cushing’s. Recurrent pituitary thyrotropinomas and prolactinomas showed moderate to high pituitary activity. In addition, in Cushing’s syndrome Ga-68-DOTATATE is useful for detection of ectopic sources of ACTH production, especially where anatomic imaging is negative.

scholarly journals The value of [68Ga]Ga-DOTA-TATE PET/CT in diagnosis and management of suspected pituitary tumors

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Fuad Novruzov ◽  
Aziz Aliyev ◽  
Ming Young S. Wan ◽  
Rizwan Syed ◽  
Elnur Mehdi ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Somatostatin Receptor ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Receptor Subtype ◽  
Somatostatin Analogue ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Pet Ct

Abstract Background Gallium 68-tetraazacyclododecane-tetraacetic acid-octreotate ([68Ga]Ga-DOTA-TATE) is a selective somatostatin analogue ligand, which shows increased affinity for somatostatin receptor subtype (SSTR) 2 and has been used routinely for imaging neuroendocrine tumors with PET/CT. We investigated the utility of [68Ga]Ga-DOTA-TATE positron emission tomography/computed tomography (PET/CT) in patients with suspected pituitary pathology. We reviewed imaging for twenty consecutive patients (8 men, 12 women, mean age of 48.2, range 14–78) with suspected pituitary pathology who were referred for [68Ga]Ga-DOTA-TATE PET/CT. Results Nine patients presented with recurrent Cushing’s syndrome following surgical resection of pituitary adenomas due to recurrent Cushing’s disease (seven patients) and ectopic ACTH secreting tumor (2 patients). All seven patients with recurrent Cushing’s disease showed positive pituitary [68Ga]Ga-DOTA-TATE uptake while both cases of ectopic hormonal secretion had absented pituitary uptake. In 1 of these 2 patients, [68Ga]Ga-DOTA-TATE was able to localize the source of ectopic ACTH tumor. Six patients presented de novo with Cushing’s due to ectopic ACTH secretion; [68Ga]Ga-DOTA-TATE PET/CT was able to localize ectopic tumors in six of eight patients (3 lungs, 2 pancreases, 1 mid-gut) There was high uptake [68Ga]Ga-DOTA-TATE in 3 cases of recurrent central hyperthyroidism (SUVmax 6.6–14.3) and 2 cases of prolactinoma (SUVmax 5.5 and 11.3). Conclusion Absent [68Ga]Ga-DOTA-TATE activity in the pituitary fossa is useful in excluding pituitary disease in recurrent Cushing’s. Recurrent pituitary thyrotropinomas and prolactinomas showed moderate to high pituitary activity. In addition, in Cushing’s syndrome, [68Ga]Ga-DOTA-TATE is useful for detection of ectopic sources of ACTH production, especially where anatomic imaging is negative.

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